Spinal interaction between the highly selective µ agonist DAMGO and several δ opioid receptor ligands in naive and morphine-tolerant mice.

Since the discovery of opioid receptor dimers their possible roles in opioid actions were intensively investigated. Here we suggest a mechanism that may involve the µ-δ opioid heterodimers. The exact role of δ opioid receptors in antinociception and in the development of opioid tolerance is still unclear. While receptor up-regulation can be observed during the development of opioid tolerance no µ receptor down-regulation could be detected within five days. In our present work we investigated how the selective δ opioid receptor agonists and antagonists influence the antinociceptive effect of the selective µ receptor agonist DAMGO in naïve and morphine-tolerant mice. We treated male NMRI mice with 200 µmol/kg subcutaneous (s.c.) morphine twice daily for three days. On the fourth day we measured the antinociceptive effect of DAMGO alone and combined with delta ligands: DPDPE, deltorphin II (agonists), TIPP and TICPψ (antagonists), respectively, administered intrathecally (i.t.) in mouse tail-flick test. In naive control mice none of the δ ligands caused significant changes in the antinociceptive action of DAMGO. The treatment with s.c. morphine resulted in approximately four-fold tolerance to i.t. DAMGO, i.e. the ED50 value of DAMGO was four times as high as in naive mice. 500 and 1000 pmol/mouse of the δ1 selective agonist DPDPE enhanced the tolerance to DAMGO while 1000 pmol/mouse of the δ2 selective agonist deltorphin II did not influence the degree of tolerance. However, both δ antagonists TIPP and TICPψ potentiated the antinociceptive effect of i.t. DAMGO, thus they restored the potency of DAMGO to the control level. The inhibitory action of DPDPE against the antinociceptive effect of DAMGO could be antagonized by TIPP and TICPψ. We hypothesize that during the development of morphine tolerance the formation of µÎ´ heterodimers may contribute to the spinal opioid tolerance. δ ligands may affect the dimer formation differently. Those, like DPDPE may facilitate the dimer formation hence inhibit the antinociceptive effect of DAMGO by causing virtual µ receptor down-regulation. Ligands that do not affect the dimer formation do not influence antinociception either but ligands with the presumed capability of disconnecting the dimers may decrease the spinal tolerance to DAMGO.

Behavioural changes in rats treated with a neurotoxic dose regimen of dextrorotatory amphetamine derivatives.

Repeated administration of amphetamine derivatives is reported to induce neurotoxicity in rat brain. Methamphetamine (MA) impairs the function of both the dopaminergic and serotonergic systems, 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) affects primarily the latter system. The neurochemical deficits induced by these amphetamines have been described in detail, but relatively few data have been reported regarding the behavioural consequences of the neurotoxic treatment. The aim of the present study was to investigate short- and long-term behavioural consequences of treatment with neurotoxic doses of (+)MA or (+)MDMA. Spontaneous locomotor activity in novel surroundings and cognitive function (avoidance behaviour) were evaluated. Rats were treated with four s.c. injections of 10 mg/kg (+)MA or (+)MDMA with a 2-hour interval between each injection. Behavioural tests were then carried out 3 days, 1, 2 and 4 weeks after these treatments. A reduction of spontaneous locomotor activity in novel surroundings was detected 3 days after the treatment with the study drugs, but not after 1, 2 and 4 weeks. No change in passive and active avoidance learning was observed. The lack of marked behavioural changes after a neurotoxic dose regimen indicates that some compensatory mechanisms may develop and counterbalance the neurochemical changes induced by these amphetamine compounds.

[Surgical management of a pleiomorphic adenoma of unusual location]. / Ritka lokalizációjú pleiomorph adenoma operált esete.

The authors describe the occurrence of a parotid pleiomorphic adenoma in an unusual location, beginning in the small salivary gland of the lower lip. The location of the pleiomorph adenoma is rare as mentioned in the bibliography, however, not demonstrated with many actual cases.

Serotonin-mediated behavior in rats chronically treated with (-) deprenyl.

(-) Deprenyl given in small (0.25 mg/kg) daily doses for 30 days to rats left the serotonin (5-HT) and the 5-hydroxyindoleacetic acid (5-HIAA) levels in the striatum unchanged. The postsynaptic 5-HT receptor responsiveness, as measured with 5-methoxy-N,N-dimethyl-tryptamine (5-MeODMT), remained also unaltered. In (-) deprenyl-treated rats the p-chloroamphetamine (PCA)-induced 5-HT syndrome was significantly increased and this enhancement of the PCA effect was not abolished by the reserpine-induced depletion of the 5-HT stores.

The anorectic effect of satietin is unrelated to carbohydrate metabolism.

The effect of satietin and amphetamine on the carbohydrate metabolism of free fed and food deprived rats was studied. Rats deprived of food for 96 hours maintained normal glucose and glucagon blood levels but the blood concentration of insulin dropped from 232.02 +/- 23.93 to 12.48 +/- 0.71 pmol/l. Amphetamine (500 micrograms/animal, intracerebroventricularly) left in normally fed rats the blood concentration of glucose, insulin and glucagon unchanged. The same treatment, however, increased the insulin concentration in the blood of food deprived rats from 11.37 +/- 4.43 to 73.47 +/- 8.29 pmol/l. Glucose and glucagon, as well as insulin levels remained unchanged in both normally fed and food deprived rats when treated with satietin (20 micrograms/rat, intracerebroventricularly). It was concluded that the anorectic effect of satietin is unrelated to carbohydrate metabolism.